WO2024104345A1 - Pyridazinone derivative and use thereof - Google Patents

Abstract

Provided are a pyridazinone derivative and use thereof. The pyridazinone derivative is represented by general formula (I). The compound of general formula (I) has activity on various fungal diseases and bacterial diseases in the agricultural field, and can be used as a fungicide/bactericide in the agricultural field.

Description

A pyridazinone derivative and its use Technical Field

The invention belongs to the field of agricultural fungicides and bactericides, and specifically relates to a pyridazinone derivative and a use thereof.

Background technique

Plant bacterial diseases are the third largest type of plant diseases after fungal diseases and viral diseases, which are caused by bacteria infecting plants. Bacterial diseases such as citrus canker, cucumber angular leaf spot, tomato bacterial wilt, rice bacterial leaf streak, and rice white leaf blight are all important diseases in the world. In my country, bacterial diseases often occur and tend to occur more frequently, with the characteristics of rapid onset, great harm, and wide distribution. Due to the long-term use of traditional bactericides such as inorganic copper preparations and antibiotics, plant pathogens have developed a certain resistance to them, and the prevention and control effect is not ideal, causing great losses to agricultural production. Therefore, the market is in urgent need of new bacterial disease control agents that are efficient, low-toxic, and environmentally friendly.

Summary of the invention

To solve the above problems, the present invention aims to provide a pyridazinone derivative and a preparation method and use thereof.

To achieve the above object, the technical solution of the present invention is as follows:

A pyridazinone derivative, a compound represented by general formula I,

Where:

_R1 is selected from halogen;

_R2 is selected from hydrogen, halogen, nitro, cyano, cyano _C1 - _C12 alkyl, _C3 - _C12 cycloalkyl, _C3 - _C12 epoxyalkyl, _C1 - _C12 alkyl, _C3 - _C12 cycloalkylmethylene, halogenated C1- _C12 alkyl _{, C1} - _C12 alkoxy _{C1 - C12} alkyl, hydroxy C1- _C12 alkyl, _C2 - _C12 alkenyl, C2 _{- C12} alkynyl, halogenated _C2 - _C12 alkenyl, halogenated _C2 - _C12 alkynyl, C1- _C12 alkoxycarbonyl, _C1 - _C12 alkoxycarbonyl _C1 - _C12 alkyl or dimethylamino C1- _C12 alkyl, aryl _{, aryl C1} - _C4 alkyl, heteroaryl, heteroaryl C1 _{- C12 4} alkyl;

_R3 is selected from hydrogen, halogen, hydroxyl, mercapto, amino, cyano, nitro, _C1 - _C12 alkyl, halogenated C1- _C12 alkyl, _C1 - _C12 alkoxy, halogenated _C1 - _C12 alkoxy, _C1 - _C12 alkylthio, halogenated _C1 - _{C12 alkylthio} , _C3 - _C12 cycloalkyl, _C1 - _C12 alkylamino;

n is 1, 2 or 3;

M is selected from Li, Na, K, Zn, Cu, Mn, Fe, Co, Mg, Ca, Cr, Mo, Ni, Sn or Se.

Preferably, in the compound of formula I,

_R1 is selected from halogen;

_R2 is selected from hydrogen, halogen, nitro, cyano, cyano _C1 - _C8 alkyl, _C3 - _C8 cycloalkyl, _{C3 - C8 epoxyalkyl, C1-C8 alkyl , C3} - _C8 cycloalkylmethylene, halogenated C1- _C8 alkyl, _C1 - _C8 alkoxy C1 _{- C8} alkyl _, hydroxy C1- _C8 alkyl, _C2 - _C8 alkenyl, _C2 - _C8 alkynyl, halogenated _C2 - _C8 alkenyl, halogenated C2- _C8 alkynyl, _C1 - _C8 alkoxycarbonyl, _C1 - _C8 alkoxycarbonyl _C1 - _C8 alkyl or dimethylamino _C1 - _C8 alkyl, aryl, arylmethylene _, heteroaryl, heteroarylmethylene which are unsubstituted or substituted by 1 to 3 _R3 ;

_R3 is selected from hydrogen, halogen, hydroxyl, mercapto, amino, cyano, nitro, C1-C8 alkyl, halogenated _C1 - _{C8 alkyl} , _C1 - _C8 alkoxy, halogenated _C1 - _C8 alkoxy, _C1 - _C8 alkylthio, halogenated _{C1 - C8} alkylthio, _C3 - _C8 cycloalkyl, _C1 - _C8 alkylamino;

n is 1, 2 or 3;

M is selected from Li, Na, K, Zn, Cu, Mn, Fe, Co, Mg, Ca, Cr, Mo, Ni, Sn or Se.

More preferably, the compound of formula I

_R1 is selected from halogen;

_R2 is selected from hydrogen, halogen, nitro, cyano, cyano _C1 - _C4 alkyl, _C3 - _C4 cycloalkyl, _C3 - _C4 epoxyalkyl, _C1 - _C4 alkyl, _C3 - _C4 cycloalkylmethylene, halogenated C1- _C4 alkyl, _C1 - _C4 alkoxy _{C1 - C4} alkyl _, hydroxy C1- _C4 alkyl, _C2 - _C4 alkenyl, _C2 - _C4 alkynyl, halogenated _{C2 - C4} alkenyl, halogenated _C2 - _C4 alkynyl, _C1 - _C4 alkoxycarbonyl, _C1 - _C4 alkoxycarbonyl _C1 - _C4 alkyl or dimethylamino C1- _C4 alkyl, aryl, arylmethylene, heteroarylmethylene which are unsubstituted or substituted by 1-2 _R3 ;

_R3 is selected from hydrogen, halogen, hydroxyl, mercapto, amino, cyano, nitro, C1- _{C4 alkyl, halogenated C1-C4 alkyl , C1-C4 alkoxy, halogenated C1-C4 alkoxy, C1-C4 alkylthio, halogenated C1-C4 alkylthio , C3 - C4 cycloalkyl , C1 - C4 alkylamino ;}

n is 1, 2 or 3;

M is selected from Li, Na, K, Zn, Cu, Mn, Fe, Co, Mg, Ca, Cr, Mo, Ni, Sn or Se.

Still further preferably, the compound of formula I

_R1 is selected from fluorine, chlorine, bromine or iodine;

_R2 is selected from hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, cyano _C1 - _C4 alkyl, _C3 - _C4 cycloalkyl _, C3- _C4 epoxyalkyl, _C1 - _C4 alkyl, _C3 - _{C4 cycloalkylmethylene, halogenated C1-C4 alkyl , C1 - C4} alkoxy _C1 - _C4 alkyl, hydroxy C1- _C4 alkyl, _C2 - _C4 alkenyl, _C2 - _C4 alkynyl, _C1 - _C4 alkoxycarbonyl, _C1 - _C4 alkoxycarbonyl _C1 - _C4 alkyl or dimethylamino _C1 - _C4 alkyl, aryl substituted with one _R3 , arylmethylene, heteroarylmethylene;

_R3 is selected from hydrogen, halogen, hydroxyl, mercapto, amino, cyano, nitro, C1-C4 alkyl, halogenated _{C1 - C4} alkyl, _C1 - _C4 alkoxy, halogenated _C1 - _C4 alkoxy, _C1 - _C4 alkylthio, halogenated _C1 - _{C4 alkylthio} ;

n is 1, 2 or 3;

M is selected from K, Na, Ca, Mg, Fe, Mn, Zn, Cu, Se.

More preferably, the compound of formula I

_R1 is selected from chlorine and bromine;

_R is selected from hydrogen, chlorine, bromine, nitro, cyano, cyanoethyl, cyclopropyl, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, cyclopropylmethylene, monofluoromethyl, monochloromethyl, difluoromethyl, dichloromethyl, trifluoromethyl, trichloromethyl, trifluoroethyl, pentafluoroethyl, heptafluoroisopropyl, methoxymethylene, methoxyethyl, ethoxymethylene, hydroxyethyl, allyl, propargyl, methoxycarbonyl, methoxycarbonylmethylene or dimethylaminomethylene, phenyl, benzyl, 2-chloropyridin-5-methylene, 2-chloro-thiazole-5-methylene, furan-2-methylene;

n is 1, 2 or 3;

M is selected from K, Na, Ca, Mg, Fe, Mn, Zn, Cu, Se.

A method for preparing the compound of general formula I, the reaction formula is as follows:

When M is Li, Na or K, the compound of formula I can be prepared by reacting the intermediate V with a base containing Li, Na or K in a suitable solvent to obtain the corresponding compound of formula I.

When M is Zn, Cu, Mn, Mg, Ca, Fe, Co, Cr, Mo, Ni, Sn or Se, the intermediate V can be reacted with an inorganic salt containing Zn, Cu, Mn, Mg, Ca, Fe, Co, Cr, Mo, Ni, Sn or Se in a suitable solvent under alkaline conditions to obtain the corresponding compound of formula I.

A pyridazinone derivative is used for preparing fungicides and bactericides in agriculture or other fields.

A use of the intermediate (V) compound as a fungicide or bactericide in agriculture or forestry.

In the definition of compounds of general formula I given above, the terms used are generally defined as follows:

Halogen: refers to fluorine, chlorine, bromine or iodine. Alkyl: straight chain or branched alkyl, such as methyl, ethyl, propyl, isopropyl, n-butyl or tert-butyl. Cycloalkyl: substituted or unsubstituted cyclic alkyl, such as cyclopropyl, cyclopentyl or cyclohexyl. Substituents such as methyl, halogen, etc. Cyanoalkyl: CNCH ₂ -, CNCH ₂ CH ₂ -. Cycloalkylmethylene: e.g. Haloalkyl: straight or branched chain alkyl, hydrogen atoms on these alkyl groups may be partially or completely replaced by halogen atoms, for example, chloromethyl, dichloromethyl, trichloromethyl, fluoromethyl, difluoromethyl, trifluoromethyl, etc. Alkoxy: straight or branched chain alkoxy. Alkoxyalkyl: straight or branched chain alkoxyalkyl, for example, CH ₃ OCH ₂ -. Hydroxyalkyl: HOCH ₂ -HOCH ₂ CH ₂ -. Haloalkoxy: straight or branched chain alkoxy, hydrogen atoms on these alkoxy groups may be partially or completely replaced by halogen atoms. For example, chloromethoxy, dichloromethoxy, trichloromethoxy, fluoromethoxy, difluoromethoxy, trifluoromethoxy, chlorofluoromethoxy, trifluoroethoxy, etc. Alkylthio: alkyl-S-, for example, CH ₃ S-. Haloalkylthio: hydrogen atoms on the alkyl group of alkylthio may be partially or completely replaced by halogen atoms, such as ClCH ₂ CH ₂ S-, CF ₃ CH ₂ S-, etc. Alkoxycarbonyl: alkoxycarbonyl-, for example CH ₃ OCO-. Alkoxycarbonylalkyl: alkoxycarbonyl-alkyl-, for example CH ₃ OCOCH ₂ -. Alkylamino: straight chain or branched alkyl, connected to the structure via a nitrogen atom bond. Dialkylaminoalkyl: such as (CH ₃ ) ₂ NCH ₂ -, (CH ₃ CH ₂ ) ₂ NCH ₂ -. Alkenyl: straight chain or branched alkenes, such as vinyl, 1-propenyl, 2-propenyl and different butenyl, pentenyl and hexenyl isomers. Alkenyl also includes polyenes, such as 1,2-propadienyl and 2,4-hexadienyl. Alkynyl: straight chain or branched alkynes, such as ethynyl, 1-propynyl, 2-propynyl and different butynyl, pentynyl and hexynyl isomers. Alkynyl also includes groups composed of multiple triple bonds, such as 2,5-hexadiynyl. Haloalkenyl: straight or branched alkenes, the hydrogen atoms on these alkenyls may be partially or completely replaced by halogen atoms. Haloalkynyl: straight or branched alkynes, the hydrogen atoms on these alkynyls may be partially or completely replaced by halogen atoms. (Hetero)aryl C ₁ -C ₄ alkyl: such as benzyl, phenethyl, p-chlorobenzyl, 2-chloropyridine-5-methylene, 3-chloro-5-trifluoromethyl-pyridine-2-ethylidene, 2-chloro-thiazol-5-methylene, etc. The aryl part of aryl, arylmethylene, heteroaryl, heteroarylmethylene includes phenyl or naphthyl, etc.; the heteroaryl part is a five-membered ring or a six-membered ring containing one or more N, O, S heteroatoms, such as furanyl, pyrazolyl, thiazolyl, pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, triazinyl, quinolyl, etc. Arylmethylene such as benzyl, p-chlorobenzyl Heteroarylmethylene such as 2-chloropyridin-5-methylene 2-Chloro-thiazole-5-methylene Furan-2-methylene wait.

Some of the compounds of the general formula I of the present invention can be illustrated by the specific compounds listed in Tables 1 to 72, but the present invention is not limited thereto.

When R ₁ ＝Cl, R ₂ ＝H, the substituents of M and n are shown in Table 1, and the representative compounds are numbered 1-1 to 1-16.

Table 1

Table 2: In general formula I, when R ₁ =Cl, R ₂ =CH ₃ , the substituents M and n are consistent with the substituents shown in Table 1, corresponding to 1-1 to 1-16 in Table 1, and the representative compound numbers are 2-1 to 2-16.

Table 3: In general formula I, when R ₁ =Cl, R ₂ =CH ₂ CH ₃ , the substituents M and n are consistent with the substituents shown in Table 1, corresponding to 1-1 to 1-16 in Table 1, and the representative compound numbers are 3-1 to 3-16.

Table 4: In general formula I, when R ₁ ＝Cl, R ₂ ＝CH ₂ CH ₂ CH ₃ , the substituents M and n are consistent with the substituents shown in Table 1, corresponding to 1-1 to 1-16 in Table 1, and the representative compound numbers are 4-1 to 4-16.

Table 5: In general formula I, when R ₁ ＝Cl, R ₂ ＝CH ₂ CH ₂ CH ₂ CH ₃ , the substituents M and n are consistent with the substituents shown in Table 1, corresponding to 1-1 to 1-16 in Table 1, and the representative compound numbers are 5-1 to 5-16.

Table 6: In general formula I, when R ₁ =Cl, R ₂ =CH(CH ₃ ) ₂ , the substituents M and n are consistent with the substituents shown in Table 1, corresponding to 1-1 to 1-16 in Table 1, and the representative compound numbers are 6-1 to 6-16.

Table 7: In general formula I, when R ₁ =Cl, R ₂ =C(CH ₃ ) ₃ , the substituents M and n are consistent with the substituents shown in Table 1, corresponding to 1-1 to 1-16 in Table 1, and the representative compound numbers are 7-1 to 7-16.

Table 8: In general formula I, when R ₁ =Cl, R ₂ =cyclopropyl, the substituents M and n are consistent with the substituents shown in Table 1, corresponding to 1-1 to 1-16 in Table 1, and the representative compound numbers are 8-1 to 8-16.

Table 9: In general formula I, when R ₁ =Cl, R ₂ =cyclopropylmethylene, the substituents M and n are consistent with the substituents shown in Table 1, corresponding to 1-1 to 1-16 in Table 1, and the representative compound numbers are 9-1 to 9-16.

Table 10: In general formula I, when R ₁ =Cl, R ₂ =isobutyl, the substituents M and n are consistent with the substituents shown in Table 1, corresponding to 1-1 to 1-16 in Table 1, and the representative compound numbers are 10-1 to 10-16.

Table 11: In general formula I, when R ₁ =Cl, R ₂ =sec-butyl, the substituents M and n are consistent with the substituents shown in Table 1, corresponding to 1-1 to 1-16 in Table 1, and the representative compound numbers are 11-1 to 11-16.

Table 12: In general formula I, when R ₁ ＝Cl, R ₂ ＝CH ₂ F, the substituents M and n are consistent with the substituents shown in Table 1, corresponding to 1-1 to 1-16 in Table 1, and the representative compound numbers are 12-1 to 12-16.

Table 13: In general formula I, when R ₁ ＝Cl, R ₂ ＝CH ₂ Cl, the substituents M and n are consistent with the substituents shown in Table 1, corresponding to 1-1 to 1-16 in Table 1, and the representative compound numbers are 13-1 to 13-16.

Table 14: In general formula I, when R ₁ =Cl, R ₂ =CHF ₂ , the substituents M and n are consistent with the substituents shown in Table 1, corresponding to 1-1 to 1-16 in Table 1, and the representative compound numbers are 14-1 to 14-16.

Table 15: In general formula I, when R ₁ ＝Cl, R ₂ ＝CHCl ₂ , the substituents M and n are consistent with the substituents shown in Table 1, corresponding to 1-1 to 1-16 in Table 1, and the representative compound numbers are 15-1 to 15-16.

Table 16: In general formula I, when R ₁ =Cl, R ₂ =CF ₃ , the substituents M and n are consistent with the substituents shown in Table 1, in order Corresponding to 1-1 to 1-16 in Table 1, the representative compound numbers are 16-1 to 16-16, respectively.

Table 17: In general formula I, when R ₁ =Cl, R ₂ =CCl ₃ , the substituents M and n are consistent with the substituents shown in Table 1, corresponding to 1-1 to 1-16 in Table 1, and the representative compound numbers are 17-1 to 17-16.

Table 18: In general formula I, when R ₁ =Cl, R ₂ =CH ₂ CF ₃ , the substituents M and n are consistent with the substituents shown in Table 1, corresponding to 1-1 to 1-16 in Table 1, and the representative compound numbers are 18-1 to 18-16.

Table 19: In general formula I, when R ₁ =Cl, R ₂ =CHF(CF ₃ ) ₂ , the substituents M and n are consistent with the substituents shown in Table 1, corresponding to 1-1 to 1-16 in Table 1, and the representative compound numbers are 19-1 to 19-16.

Table 20: In general formula I, when R ₁ =Cl, R ₂ =CH ₂ OCH ₃ , the substituents M and n are consistent with the substituents shown in Table 1, corresponding to 1-1 to 1-16 in Table 1, and the representative compound numbers are 20-1 to 20-16.

Table 21: In general formula I, when R ₁ ＝Cl, R ₂ ＝CH ₂ CH ₂ OCH ₃ , the substituents M and n are consistent with the substituents shown in Table 1, corresponding to 1-1 to 1-16 in Table 1, and the representative compound numbers are 21-1 to 21-16.

Table 22: In general formula I, when R ₁ ＝Cl, R ₂ ＝CH ₂ CH＝CH ₂ , the substituents M and n are consistent with the substituents shown in Table 1, corresponding to 1-1 to 1-16 in Table 1, and the representative compound numbers are 22-1 to 22-16.

Table 23: In general formula I, when R ₁ ＝Cl, R ₂ ＝CH ₂ C≡CH, the substituents M and n are consistent with the substituents shown in Table 1, corresponding to 1-1 to 1-16 in Table 1, and the representative compound numbers are 23-1 to 23-16.

Table 24: In general formula I, when R ₁ =Cl, R ₂ =CH ₂ COOCH ₃ , the substituents M and n are consistent with the substituents shown in Table 1, corresponding to 1-1 to 1-16 in Table 1, and the representative compound numbers are 24-1 to 24-16.

Table 25: In general formula I, when R ₁ =Cl, R ₂ =COOCH ₃ , the substituents M and n are consistent with the substituents shown in Table 1, corresponding to 1-1 to 1-16 in Table 1, and the representative compound numbers are 25-1 to 25-16.

Table 26: In general formula I, when R ₁ ＝Cl, R ₂ ＝Ph, the substituents M and n are consistent with the substituents shown in Table 1, corresponding to 1-1 to 1-16 in Table 1, and the representative compound numbers are 26-1 to 26-16.

Table 27: In general formula I, when R ₁ ＝Cl, R ₂ ＝CH ₂ Ph, the substituents M and n are consistent with the substituents shown in Table 1, corresponding to 1-1 to 1-16 in Table 1, and the representative compound numbers are 27-1 to 27-16.

Table 28: In general formula I, when R ₁ =Cl, R ₂ =5-CH ₂ -2-Cl-Pyridine, the substituents M and n are consistent with the substituents shown in Table 1, corresponding to 1-1 to 1-16 in Table 1, and the representative compound numbers are 28-1 to 28-16.

Table 29: In general formula I, when R ₁ =Cl, R ₂ =5-CH ₂ -2-Cl-Thiazole, the substituents M and n are consistent with the substituents shown in Table 1, corresponding to 1-1 to 1-16 in Table 1, and the representative compound numbers are 29-1 to 29-16.

Table 30: In general formula I, when R ₁ =Cl, R ₂ =2-CH ₂ -Furan, the substituents M and n are consistent with the substituents shown in Table 1, corresponding to 1-1 to 1-16 in Table 1, and the representative compound numbers are 30-1 to 30-16.

Table 31: In general formula I, when R ₁ ＝Cl, R ₂ ＝Cl, the substituents M and n are consistent with the substituents shown in Table 1, corresponding to 1-1 to 1-16 in Table 1, and the representative compound numbers are 31-1 to 31-16, respectively.

Table 32: In general formula I, when R ₁ ＝Cl, R ₂ ＝Br, the substituents M and n are consistent with the substituents shown in Table 1, corresponding to 1-1 to 1-16 in Table 1, and the representative compound numbers are 32-1 to 32-16.

Table 33: In general formula I, when R ₁ ＝Cl, R ₂ ＝CN, the substituents M and n are consistent with the substituents shown in Table 1, corresponding to 1-1 to 1-16 in Table 1, and the representative compound numbers are 33-1 to 33-16.

Table 34: In general formula I, when R ₁ =Cl, R ₂ =NO ₂ , the substituents M and n are consistent with the substituents shown in Table 1, corresponding to 1-1 to 1-16 in Table 1, and the representative compound numbers are 34-1 to 34-16.

Table 35: In general formula I, when R ₁ ＝Cl, R ₂ ＝CH ₂ CN, the substituents M and n are consistent with the substituents shown in Table 1, corresponding to 1-1 to 1-16 in Table 1, and the representative compound numbers are 35-1 to 35-16.

Table 36: In general formula I, when R ₁ ＝Br, R ₂ ＝H, the substituents M and n are consistent with the substituents shown in Table 1, corresponding to 1-1 to 1-16 in Table 1, and the representative compound numbers are 36-1 to 36-16.

Table 37: In general formula I, when R ₁ =Br, R ₂ =CH ₃ , the substituents M and n are consistent with the substituents shown in Table 36, corresponding to 1-1 to 1-16 in Table 1, and the representative compound numbers are 37-1 to 37-16.

Table 38: In general formula I, when R ₁ =Br, R ₂ =CH ₂ CH ₃ , the substituents M and n are consistent with the substituents shown in Table 36, corresponding to 1-1 to 1-16 in Table 1, and the representative compound numbers are 38-1 to 38-16.

Table 39: In general formula I, when R ₁ =Br, R ₂ =CH ₂ CH ₂ CH ₃ , the substituents M and n are consistent with the substituents shown in Table 36, corresponding to 1-1 to 1-16 in Table 1, and the representative compound numbers are 39-1 to 39-16.

Table 40: In general formula I, when R ₁ ＝Br, R ₂ ＝CH ₂ CH ₂ CH ₂ CH ₃ , the substituents M and n are consistent with the substituents shown in Table 36, corresponding to 1-1 to 1-16 in Table 1, and the representative compound numbers are 40-1 to 40-16, respectively.

Table 41: In general formula I, when R ₁ =Br, R ₂ =CH(CH ₃ ) ₂ , the substituents M and n are consistent with the substituents shown in Table 36, corresponding to 1-1 to 1-16 in Table 1, and the representative compound numbers are 41-1 to 41-16.

Table 42: In general formula I, when R ₁ =Br, R ₂ =C(CH ₃ ) ₃ , the substituents M and n are consistent with the substituents shown in Table 36, corresponding to 1-1 to 1-16 in Table 1, and the representative compound numbers are 42-1 to 42-16.

Table 43: In general formula I, when R ₁ =Br, R ₂ =cyclopropyl, the substituents M and n are consistent with the substituents shown in Table 36, corresponding to 1-1 to 1-16 in Table 1, and the representative compound numbers are 43-1 to 43-16.

Table 44: In general formula I, when R ₁ =Br, R ₂ =cyclopropylmethylene, the substituents M and n are consistent with the substituents shown in Table 36, corresponding to 1-1 to 1-16 in Table 1, and the representative compound numbers are 44-1 to 44-16.

Table 45: In general formula I, when R ₁ =Br, R ₂ =isobutyl, the substituents M and n are consistent with the substituents shown in Table 36, corresponding to 1-1 to 1-16 in Table 1, and the representative compound numbers are 45-1 to 45-16.

Table 46: In general formula I, when R ₁ =Br, R ₂ =sec-butyl, the substituents M and n are consistent with the substituents shown in Table 36, corresponding to 1-1 to 1-16 in Table 1, and the representative compound numbers are 46-1 to 46-16.

Table 47: In general formula I, when R ₁ =Br, R ₂ =CH ₂ F, the substituents M and n are consistent with the substituents shown in Table 36, corresponding to 1-1 to 1-16 in Table 1, and the representative compound numbers are 47-1 to 47-16.

Table 48: In general formula I, when R ₁ =Br, R ₂ =CH ₂ Cl, the substituents M and n are consistent with the substituents shown in Table 36, corresponding to 1-1 to 1-16 in Table 1, and the representative compound numbers are 48-1 to 48-16.

Table 49: In general formula I, when R ₁ =Br, R ₂ =CHF ₂ , the substituents M and n are consistent with the substituents shown in Table 36, corresponding to 1-1 to 1-16 in Table 1, and the representative compound numbers are 49-1 to 49-16.

Table 50: In general formula I, when R ₁ =Br, R ₂ =CHCl ₂ , the substituents M and n are consistent with the substituents shown in Table 36, corresponding to 1-1 to 1-16 in Table 1, and the representative compound numbers are 50-1 to 50-16.

Table 51: In general formula I, when R ₁ =Br, R ₂ =CF ₃ , the substituents M and n are consistent with the substituents shown in Table 36, corresponding to 1-1 to 1-16 in Table 1, and the representative compound numbers are 51-1 to 51-16.

Table 52: In general formula I, when R ₁ =Br, R ₂ =CCl ₃ , the substituents M and n are consistent with the substituents shown in Table 36, corresponding to 1-1 to 1-16 in Table 1, and the representative compound numbers are 52-1 to 52-16.

Table 53: In general formula I, when R ₁ =Br, R ₂ =CH ₂ CF ₃ , the substituents M and n are consistent with the substituents shown in Table 36, corresponding to 1-1 to 1-16 in Table 1, and the representative compound numbers are 53-1 to 53-16.

Table 54: In general formula I, when R ₁ =Br, R ₂ =CHF(CF ₃ ) ₂ , the substituents M and n are consistent with the substituents shown in Table 36, corresponding to 1-1 to 1-16 in Table 1, and the representative compound numbers are 54-1 to 54-16.

Table 55: In general formula I, when R ₁ =Br, R ₂ =CH ₂ OCH ₃ , the substituents M and n are consistent with the substituents shown in Table 36, corresponding to 1-1 to 1-16 in Table 1, and the representative compound numbers are 55-1 to 55-16.

Table 56: In general formula I, when R ₁ =Br, R ₂ =CH ₂ CH ₂ OCH ₃ , the substituents M and n are consistent with the substituents shown in Table 36, corresponding to 1-1 to 1-16 in Table 1, and the representative compound numbers are 56-1 to 56-16.

Table 57: In general formula I, when R ₁ =Br, R ₂ =CH ₂ CH=CH ₂ , the substituents M and n are consistent with the substituents shown in Table 36, corresponding to 1-1 to 1-16 in Table 1, and the representative compound numbers are 57-1 to 57-16.

Table 58: In general formula I, when R ₁ =Br, R ₂ =CH ₂ C≡CH, the substituents M and n are consistent with the substituents shown in Table 36, corresponding to 1-1 to 1-16 in Table 1, and the representative compound numbers are 58-1 to 58-16.

Table 59: In general formula I, when R ₁ =Br, R ₂ =CH ₂ COOCH ₃ , the substituents M and n are consistent with the substituents shown in Table 36, and the representative compound numbers are 59-1 to 59-16, respectively.

Table 60: In general formula I, when R ₁ =Br, R ₂ =COOCH ₃ , the substituents M and n are consistent with the substituents shown in Table 36, corresponding to 1-1 to 1-16 in Table 1, and the representative compound numbers are 60-1 to 60-16.

Table 61: In general formula I, when R ₁ =Br, R ₂ =Ph, the substituents M and n are consistent with the substituents shown in Table 36, corresponding to 1-1 to 1-16 in Table 1, and the representative compound numbers are 61-1 to 61-16.

Table 62: In general formula I, when R ₁ =Br, R ₂ =CH ₂ Ph, the substituents M and n are consistent with the substituents shown in Table 36, corresponding to 1-1 to 1-16 in Table 1, and the representative compound numbers are 62-1 to 62-16.

Table 63: In general formula I, when R ₁ =Br, R ₂ =5-CH ₂ -2-Cl-Pyridine, the substituents M and n are consistent with the substituents shown in Table 36, corresponding to 1-1 to 1-16 in Table 1, and the representative compound numbers are 63-1 to 63-16.

Table 64: In general formula I, when R ₁ =Br, R ₂ =5-CH ₂ -2-Cl-Thiazole, the substituents M and n are consistent with the substituents shown in Table 36, corresponding to 1-1 to 1-16 in Table 1, and the representative compound numbers are 64-1 to 64-16.

Table 65: In general formula I, when R ₁ =Br, R ₂ =2-CH ₂ -Furan, the substituents M and n are consistent with the substituents shown in Table 36, corresponding to 1-1 to 1-16 in Table 1, and the representative compound numbers are 65-1 to 65-16.

Table 66: In general formula I, when R ₁ ＝Br, R ₂ ＝Cl, the substituents M and n are consistent with the substituents shown in Table 36, corresponding to 1-1 to 1-16 in Table 1, and the representative compound numbers are 66-1 to 66-16.

Table 67: In general formula I, when R ₁ =Br, R ₂ =Br, the substituents M and n are consistent with the substituents shown in Table 36, corresponding to 1-1 to 1-16 in Table 1, and the representative compound numbers are 67-1 to 67-16.

Table 68: In general formula I, when R ₁ ＝Br, R ₂ ＝CN, the substituents M and n are consistent with the substituents shown in Table 36, corresponding to 1-1 to 1-16 in Table 1, and the representative compound numbers are 68-1 to 68-16.

Table 69: In general formula I, when R ₁ =Br, R ₂ =NO ₂ , the substituents M and n are consistent with the substituents shown in Table 36, corresponding to 1-1 to 1-16 in Table 1, and the representative compound numbers are 69-1 to 69-16.

Table 70: In general formula I, when R ₁ =Br, R ₂ =CH ₂ CN, the substituents M and n are consistent with the substituents shown in Table 36, corresponding to 1-1 to 1-16 in Table 1, and the representative compound numbers are 70-1 to 70-16.

Table 71: In general formula I, when R ₁ ＝Cl, R ₂ ＝CH ₂ CH ₂ Ph, the substituents M and n are consistent with the substituents shown in Table 1, corresponding to 1-1 to 1-16 in Table 1, and the representative compound numbers are 71-1 to 71-16, respectively.

Table 72: In general formula I, when R ₁ =Br, R ₂ =CH ₂ CH ₂ Ph, the substituents M and n are consistent with the substituents shown in Table 1, corresponding to 1-1 to 1-16 in Table 1, and the representative compound numbers are 72-1 to 72-16.

Table 73: In general formula I, when R ₁ =Cl, R ₂ =CH ₂ -Ph-4-NO ₂ , the substituents M and n are consistent with the substituents shown in Table 1, corresponding to 1-1 to 1-16 in Table 1, and the representative compound numbers are 73-1 to 73-16.

Table 74: In general formula I, when R ₁ =Cl, R ₂ =CH ₂ -Ph-4-CN, the substituents M and n are the same as those shown in Table 1. Table 75: In general formula I, when R ₁ ＝Cl, R ₂ ＝CH ₂ -Ph-4-Cl, the substituents M and n are consistent with the substituents shown in Table 1, corresponding to 1-1 to 1-16 in Table 1, and the representative compound numbers are 75-1 to 75-16.

Table 76: In general formula I, when R ₁ ＝Cl, R ₂ ＝CH ₂ -Ph-2-Cl, the substituents M and n are consistent with the substituents shown in Table 1, corresponding to 1-1 to 1-16 in Table 1, and the representative compound numbers are 76-1 to 76-16.

Table 77: In general formula I, when R ₁ =Cl, R ₂ =CH ₂ -Ph-4-OCH ₃ , the substituents M and n are consistent with the substituents shown in Table 1, corresponding to 1-1 to 1-16 in Table 1, and the representative compound numbers are 77-1 to 77-16.

Table 78: In general formula I, when R ₁ =Cl, R ₂ =CH ₂ -Ph-4-C(CH ₃ ) ₃ , the substituents M and n are consistent with the substituents shown in Table 1, corresponding to 1-1 to 1-16 in Table 1, and the representative compound numbers are 78-1 to 78-16.

Table 79: In general formula I, when R ₁ ＝Cl, R ₂ ＝CH ₂ -Ph-3,4-2Cl, the substituents M and n are consistent with the substituents shown in Table 1, corresponding to 1-1 to 1-16 in Table 1, and the representative compound numbers are 79-1 to 79-16, respectively.

Table 80: In general formula I, when R ₁ =Cl, R ₂ =CH ₂ -Ph-4-CF ₃ , the substituents M and n are consistent with the substituents shown in Table 1, corresponding to 1-1 to 1-16 in Table 1, and the representative compound numbers are 80-1 to 80-16.

Table 81: In general formula I, when R ₁ ＝Cl, R ₂ ＝CH ₂ -Ph-2,4-2Cl, the substituents M and n are consistent with the substituents shown in Table 1, corresponding to 1-1 to 1-16 in Table 1, and the representative compound numbers are 81-1 to 81-16, respectively.

Table 82: In general formula I, when R ₁ ＝Cl, R ₂ ＝CH ₂ -Ph-2,6-2Cl, the substituents M and n are consistent with the substituents shown in Table 1, corresponding to 1-1 to 1-16 in Table 1, and the representative compound numbers are 82-1 to 82-16, respectively.

Table 83: In general formula I, when R ₁ ＝Cl, R ₂ ＝CH ₂ -Ph-3-Cl, the substituents M and n are consistent with the substituents shown in Table 1, corresponding to 1-1 to 1-16 in Table 1, and the representative compound numbers are 83-1 to 83-16.

Table 84: In general formula I, when R ₁ ＝Cl, R ₂ ＝2-CH ₂ -Naph, the substituents M and n are consistent with the substituents shown in Table 1, corresponding to 1-1 to 1-16 in Table 1, and the representative compound numbers are 84-1 to 84-16.

Table 85: In general formula I, when R ₁ =Cl, R ₂ =CH ₂ -Ph-4-CH ₃ , the substituents M and n are consistent with the substituents shown in Table 1, corresponding to 1-1 to 1-16 in Table 1, and the representative compound numbers are 85-1 to 85-16.

Table 86: In general formula I, when R ₁ ＝Cl, R ₂ ＝CH ₂ COPh, the substituents M and n are consistent with the substituents shown in Table 1, corresponding to 1-1 to 1-16 in Table 1, and the representative compound numbers are 86-1 to 86-16.

Some intermediates V of the present invention can be illustrated by the specific compounds listed in Table 87, but the present invention is not limited to these compounds.

Table 87

The compounds of the present invention are prepared according to the following method, and the reaction formula is as follows, wherein the groups have the same definitions as above unless otherwise specified:

When M is Li, Na, or K, the compound of formula I can be obtained by reacting the intermediate V with lithium hydroxide, sodium hydroxide, or potassium hydroxide in an organic solvent such as methanol, ethanol, toluene, xylene, or water. The molar ratio of the intermediate V to lithium hydroxide, sodium hydroxide, or potassium hydroxide is 1:1 to 1:3;

When M is Zn, Cu, Mn, Mg, Ca, Fe, Co, Cr, Mo, Ni, Sn or Se, it can be obtained by reacting the intermediate V with an inorganic salt containing a metal cation in a suitable solvent under alkaline conditions.

Suitable bases can be selected from, for example, lithium hydroxide, sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate and the like.

The reaction is carried out in a suitable solvent, which can be selected from water or an organic solvent such as methanol, ethanol, n-propanol, isopropanol, DMF, DMSO, acetonitrile, triethylamine, toluene, xylene, etc. The reaction temperature can be 0 to 100° C., usually 20 to 80° C. The reaction time is 10 minutes to 20 hours, usually 30 minutes to 8 hours.

The inorganic salt containing metal cations can be selected from zinc chloride, zinc sulfate, zinc nitrate, zinc acetate, cupric chloride, cupric sulfate, cupric acetate, cupric nitrate, manganese chloride, manganese sulfate, manganese acetate, manganese nitrate, ferric chloride, ferric sulfate, ferric nitrate, ferric acetate, ferrous chloride, ferrous sulfate, ferrous nitrate, cobalt chloride, cobalt sulfate, cobalt nitrate, cobalt acetate, magnesium chloride, magnesium sulfate, magnesium nitrate, calcium chloride, calcium sulfate, calcium carbonate, calcium nitrate, calcium acetate, chromium chloride, chromium sulfate, chromium nitrate, chromium acetate, molybdenum chloride, molybdenum sulfate, molybdenum nitrate, molybdenum acetate, nickel chloride, nickel sulfate, nickel nitrate, nickel acetate, stannous chloride or selenium dioxide, etc.

The molar ratio of the intermediate V to the appropriate base is 1:1 to 1:3;

The feeding molar ratio of the inorganic salt of divalent metal cation and V is 1:1 to 1:2;

The feeding molar ratio of the inorganic salt of trivalent metal cation and V is 1:1 to 1:3.

References for the preparation method of intermediate V: Patents, CN107964007 A, CN110483349 A; Literature, Journal of Agricultural and Food Chemistry, 2003, 51(1): 152-155; Tetrahedron Letters (2021), 68, 152950; JP60004173 A, etc.

In the compound of general formula I, the bonding mode between M and S is covalent bonding or ionic bonding, and the corresponding compound is a complex or ionic compound.

The compounds of the general formula I and the intermediate V of the present invention can be used for controlling plant diseases, and can be used for preventing and controlling diseases caused by various fungi such as oomycetes, basidiomycetes, ascomycetes and deuteromycetes on various crops, for example, oomycete diseases, such as downy mildew (cucumber downy mildew, rape downy mildew, soybean downy mildew, beet downy mildew, sugarcane downy mildew, tobacco downy mildew, pea downy mildew, loofah downy mildew, wax gourd downy mildew, melon downy mildew, cabbage downy mildew, spinach downy mildew, radish downy mildew, grape downy mildew, onion downy mildew), white rust (rape white rust, cabbage downy mildew, spinach downy mildew, radish downy mildew, grape downy mildew, onion downy mildew), White rust), damping-off (rapeseed damping-off, tobacco damping-off, tomato damping-off, pepper damping-off, eggplant damping-off, cucumber damping-off, cotton seedling damping-off), cotton rot (pepper cotton rot, loofah cotton rot, wax gourd cotton rot), blight (broad bean blight, cucumber blight, pumpkin blight, wax gourd blight, watermelon blight, melon blight, pepper blight, leek blight, garlic blight, cotton blight), late blight (potato late blight, tomato late blight), etc.; semi-common fungal diseases, such as wilt (sweet potato wilt, cotton wilt, sesame wilt, castor wilt, tomato wilt, bean blight Wilt, cucumber wilt, loofah wilt, pumpkin wilt, wax gourd wilt, watermelon wilt, melon wilt, pepper wilt, broad bean wilt, rapeseed wilt, soybean wilt), root rot (pepper root rot, eggplant root rot, kidney bean root rot, cucumber root rot, bitter melon root rot, cotton black root rot, broad bean root rot), damping-off (cotton seedling damping-off, sesame damping-off, pepper damping-off, cucumber damping-off, cabbage damping-off), anthracnose (sorghum anthracnose, cotton anthracnose, hemp anthracnose, jute anthracnose, flax anthracnose, tobacco anthracnose, mulberry anthracnose, Anthracnose of pepper, eggplant, bean, cucumber, bitter gourd, zucchini, wax gourd, watermelon, melon, litchi), Verticillium wilt (cotton, sunflower, tomato, pepper, eggplant), scab (zucchini, wax gourd, melon), gray mold (cotton boll, jute, tomato, pepper, bean, celery, spinach, kiwi), brown spot (cotton, jute, Beet brown spot, peanut brown spot, pepper brown spot, wax gourd brown spot, soybean brown spot, sunflower brown spot, pea brown spot, broad bean brown spot), black spot (false black spot of flax, rape black spot, sesame black spot, sunflower black spot, castor black spot, tomato black spot, pepper black spot, eggplant black spot, kidney bean black spot, cucumber black spot, celery black spot, carrot black rot, carrot black spot, apple black spot, peanut black spot), spot blight (tomato spot blight, pepper spot blight, celery spot blight), early blight (tomato early blight, pepper early blight, eggplant early blight) blight, potato early blight, celery early blight), ring rot (soybean ring rot, sesame ring rot, bean ring rot), leaf blight (sesame leaf blight, sunflower leaf blight, watermelon leaf blight, melon leaf blight), stem base rot (tomato stem base rot, bean stem base rot), and others (corn round spot, hemp waist break disease, rice blast, chestnut black sheath disease, sugarcane eye spot disease, cotton boll Aspergillus disease, peanut crown rot, soybean stem blight, soybean black spot disease, melon large spot disease, peanut web spot disease, tea red leaf spot disease, pepper white star disease, wax gourd leaf spot disease, celery black rot, spinach heart rot, hemp leaf mold disease , jute spot disease, jute stem spot disease, soybean purple spot disease, sesame leaf spot disease, castor gray spot disease, brown leaf spot disease, eggplant brown round star disease, kidney bean red spot disease, bitter gourd white spot disease, watermelon spot disease, jute rot, sunflower root rot, kidney bean charcoal rot, soybean target spot disease, eggplant coryneform leaf spot disease, cucumber target spot disease, tomato leaf mold, eggplant leaf mold disease, broad bean red spot disease, etc.); basidiomycete diseases, such as rust (wheat stripe rust, wheat stem rust, wheat leaf rust, flower rust, sunflower rust, sugarcane rust, leek rust, onion rust, chestnut rust, soybean rust), smut ( Corn head smut, corn smut, sorghum head smut, sorghum loose smut, sorghum hard smut, sorghum column smut, chestnut smut, sugarcane smut, bean rust) and others (such as wheat sheath blight, rice sheath blight, etc.); Ascomycete diseases, such as powdery mildew (wheat powdery mildew, rape powdery mildew, sesame powdery mildew, sunflower powdery mildew, beet powdery mildew, eggplant powdery mildew, pea powdery mildew, loofah powdery mildew, pumpkin powdery mildew, zucchini powdery mildew, wax gourd powdery mildew, melon powdery mildew, grape powdery mildew, broad bean powdery mildew), sclerotinia (flax sclerotinia, rape sclerotinia, It has a good preventive effect on soybean sclerotinia, peanut sclerotinia, tobacco sclerotinia, pepper sclerotinia, eggplant sclerotinia, kidney bean sclerotinia, pea sclerotinia, cucumber sclerotinia, bitter melon sclerotinia, wax gourd sclerotinia, watermelon sclerotinia, celery sclerotinia), black spot (apple black spot, pear black spot), etc.

The compound of the general formula I and the intermediate V of the present invention are used for controlling plant bacterial diseases, and can be used to prevent and treat a variety of plant bacterial diseases, for example: Gram-negative bacteria: Erwinia (causing apricot fire blight, etc.); Pectobacterium (causing soft rot of cruciferous vegetables, potato black leg disease, etc.); Dickie's genus (causing sweet potato stem rot, corn bacterial stem rot, rice bacterial basal rot, potato black leg disease, pear rust, etc.); Pantoea (causing corn bacterial wilt, corn Pantoea leaf spot disease, etc.); disease, bacterial leaf blight of red beans, drupe canker, etc.); Pseudomonas (causing peach canker, bacterial blight of peas, bacterial black spot of crucifers, bacterial leaf spot of tomatoes, bacterial spot of tomatoes, bacterial black spot of rapeseed, bacterial angular spot of sesame, bacterial angular spot of cucumber, wildfire of tobacco, bacterial brown spot of corn, bacterial stem blight of broad beans, bacterial spot of soybeans, bacterial leaf spot of beets, bacterial pith necrosis of tomatoes, soft rot of ginseng by Pseudomonas aeruginosa, etc.); Ralstonia (causing various bacterial wilt diseases, etc.); Burkholderia (causing bacterial wilt of carnation, onion rot, bacterial ear blight of rice, etc.); Acidovorax (causing fruit spot of melons, brown spot of orchids, brown streak of oats, bacterial leaf spot of konjac, etc.); Xanthomonas (causing bacterial leaf blight of rice, bacterial streak of rice, spot disease of pepper and tomato, scab of pepper and tomato, bacterial black spot of mango, bacterial leaf spot of pepper, bacterial blight of poinsettia, angular spot of cotton, bacterial spot of soybean disease, crucifer black rot, cassava bacterial wilt, sugarcane gummosis, anthurium bacterial blight, citrus canker, hyacinth yellow rot, peach bacterial punchhole, strawberry angular leaf spot, poplar bacterial canker, etc.); Agrobacterium (causing root cancer of Rosaceae, etc.); Xylem bacteria (causing Pierce's disease of grapes and citrus variegated chlorosis, etc.); Phloemobacter (causing citrus Huanglongbing, etc.); Enterobacter (causing poplar wilt, etc.); Xylophilus (causing grape bacterial blight, etc.).

Gram-positive bacteria: Corynebacterium (causing potato ring rot, bacterial canker of tomatoes, bacterial wilt of alfalfa, internal wilt of corn, bacterial mosaic of wheat, etc.); Streptomyces (causing potato scab, etc.); Brevibacterium (causing bacterial wilt of beans, yellow blister of tulip, bean wilt, etc.); Arthrobacter (causing American holly leaf blight, etc.); Rhodococcus (causing sweet pea banding, etc.); Bacillus (causing Bacillus leaf spot of corn, white leaf streak of wheat, etc.); Russell's bacillus (causing duckgrass honey ear disease, etc.).

BRIEF DESCRIPTION OF THE DRAWINGS

FIG1 is an infrared spectrum of intermediate V (R ₂ ＝H, R ₁ ＝Cl) provided in an embodiment of the present invention.

FIG2 is an infrared spectrum of compound 1-8 provided in an embodiment of the present invention.

FIG3 is an infrared spectrum of compound 27-9 provided in an embodiment of the present invention.

FIG4 is an infrared spectrum of compound 27-8 provided in an embodiment of the present invention.

Detailed ways

The following specific examples are used to further illustrate the present invention, but the present invention is by no means limited to these examples (unless otherwise noted, all raw materials used are commercially available).

Synthesis Example

Example 1: Preparation of Compound 1-2

1) Preparation of 4-chloro-5-mercaptopyridazinone M-1

Method 1: Add 1.65 g (0.01 mol) of 4,5-dichloropyridazinone to 40 ml of ethanol, stir under ice bath, dropwise add a pre-prepared aqueous solution containing 0.02 mol of NaSH (content of about 25% to 30%), stir for 2 h, monitor the reaction by TLC, pour the reaction solution into 500 ml of water, add 20 ml of concentrated hydrochloric acid to acidify, and obtain 1.35 g of white solid, with a yield of 83.3%. LC-MS (m/z): 162.97 ([M+1] ⁺ ), 160.96 ([M-1] ^- ).

Method 2: Add 9.90g (0.06mol) of 4,5-dichloropyridazinone to a 500ml single-necked flask containing 200ml of water, stir at room temperature (25°C) until it becomes turbid, add a pre-prepared aqueous solution containing 0.12mol of NaSH (content of about 25% to 30%), stir for 1-2h, the solution becomes yellow or reddish brown and clear, after TLC monitoring the reaction is complete, add 100ml Water, adjusted Ph=3-4 with dilute hydrochloric acid, a large amount of solid precipitated, filtered, washed with water, washed with mixed solvent (ethyl acetate: petroleum ether=1:10), dried to obtain 9.0 g of white solid, yield 92.3%. LC-MS (m/z): 162.97 ([M+1] ⁺ ), 160.96 ([M-1] ^- ).

2) 0.84 g (0.015 mol) of potassium hydroxide, 1.62 g (0.01 mol) of 4-chloro-5-mercaptopyridazinone and 20 ml of water were added to a reaction flask and stirred at room temperature for 30 minutes. The reaction solution gradually formed a yellow transparent liquid. After the reaction solution was desolvated, 20 ml of ethyl acetate and 3 ml of ethanol were added thereto. The solid was precipitated by stirring and filtered. The filter cake was washed with ethyl acetate to obtain compound 1-2, 1.6 g of a light yellow solid.

Example 2: Preparation of Compound 1-8

Method 1: 3.25 g (0.02 mol) of 4-chloro-5-mercaptopyridazinone and 100 ml of water were added to a 250 ml single-mouth reaction bottle, and 5-10 ml of an aqueous solution containing 1.23 g (0.022 mol) of potassium hydroxide was added dropwise. The mixture was stirred at room temperature for 1 hour. After the solution became a yellow transparent liquid, an aqueous solution containing 1.60 g (0.01 mol) of anhydrous copper sulfate was quickly added. The reaction liquid quickly turned dark green and turbid. After reacting for 1 hour, the solid was filtered, washed with water, and dried to obtain 3.82 g of a dark green solid. The solid was ground into powder, and then refluxed with 20 ml of ethanol for 1 hour. The solid was filtered and dried to obtain 3.59 g of compound 1-8.

Method 2: 8.80 g (0.22 mol) of sodium hydroxide and 400 ml of water were added to a 1000 ml three-necked reaction flask, and then 32.5 g (0.20 mol) of 4-chloro-5-mercaptopyridazinone was added. After stirring at room temperature to dissolve it into a yellow transparent liquid, 400 ml of an aqueous solution containing 16.0 g (0.10 mol) of anhydrous copper sulfate was quickly added. The reaction liquid quickly turned dark green and turbid. After reacting for 1-2 hours, the solid was filtered, washed with water, and dried to obtain 38.4 g of a dark green solid. The solid was ground into powder, and then refluxed with 400 ml of ethanol for 1 hour. The solid was filtered and dried to obtain 35.7 g of compound 1-8.

Method 3: 8.13 g (0.05 mol) of 4-chloro-5-mercaptopyridazinone and 200 ml of water were added to a 500 ml single-mouth reaction bottle, and 20 ml of an aqueous solution containing 3.08 g (0.055 mol) of potassium hydroxide was added dropwise. The mixture was stirred at room temperature for 1 hour. After the solution became a yellow transparent liquid, an aqueous solution containing 4.26 g (0.025 mol) of CuCl ₂ ·2H ₂ O was quickly added. The reaction liquid quickly turned dark green and turbid. After reacting for 1 hour, the solid was filtered, washed with water, and dried to obtain 9.80 g of a dark green solid. The solid was ground into powder, and then refluxed with 200 ml of ethanol for 1 hour. The solid was filtered and dried to obtain 9.60 g of compound 1-8.

Method 1 Amplification: 130.0 g (0.80 mol) of 4-chloro-5-mercaptopyridazinone and 2000 ml of water were added to a 5L three-necked reaction flask, mechanical stirring was started, 1000 ml of an aqueous solution containing 49.28 g (0.88 mol) of potassium hydroxide was added, and the mixture was stirred at room temperature until the solution was clear. 63.84 g (0.40 mol) of anhydrous copper sulfate was dissolved in 1000 ml of water and then quickly added to the reaction solution for 2 hours. The reaction solution quickly turned dark green and turbid. The solid was filtered, washed with water, and dried to obtain 151.6 g of a yellow-green solid. The solid was ground into powder, and then refluxed with 1000 ml of ethanol for 1 hour. The solid was filtered and dried to obtain 144.2 g of compound 1-8.

Example 3: Preparation of Compound 27-9

1) Preparation of 4,5-dichloro-1-benzylpyridazinone

1.65 g (0.01 mol) of 4,5-dichloropyridazinone, 2.07 g (0.015 mol) of potassium carbonate and 1.26 g (0.01 mol) of benzyl chloride were added to 40 ml of DMF, stirred at 90°C for 4 hours, and after the reaction was completed by TLC monitoring, the reaction solution was cooled and poured into water, extracted with ethyl acetate, and concentrated. The residue was subjected to column chromatography to obtain 2.35 g of a white solid, with a yield of 92.5%. LC-MS (m/z): 255.01 ([M+1] ⁺ ), 252.99 ([M-1] ^- ).

2) Preparation of 4-chloro-5-mercapto-1-benzylpyridazinone M-27

2.54 g (0.01 mol) of 4,5-dichloro-1-benzylpyridazinone was added to 40 ml of DMF, stirred under ice bath, and a pre-prepared aqueous solution containing 0.03 mol of NaSH (mass percentage of about 25% to 30%) was added dropwise. After stirring for 30 minutes, after the reaction was completed by TLC monitoring, the reaction solution was poured into 500 ml of water and acidified with 20 ml of concentrated hydrochloric acid to obtain 2.17 g of white solid, with a yield of 86.0%. LC-MS (m/z): 253.02 ([M+1] ⁺ ), 251.00 ([M-1] ^- ).

3) 0.62 g (0.015 mol) potassium hydroxide, 2.52 g (0.01 mol) 4-chloro-5-mercapto-1-benzylpyridazinone and 50 ml Water was added to the reaction flask and reacted at room temperature for 30 minutes. After the solution became a yellow transparent liquid, a mixture of 0.80 g (0.005 mol) zinc sulfate and 5 ml water was added dropwise. The reaction solution quickly turned white and turbid. After continuing the reaction for 1 hour, the solid was filtered and washed with water to obtain compound 27-9, a white solid of 2.65 g. LC-MS (m/z): 564.94 ([M-1] ^- ).

Meanwhile, other compounds represented by the general formula I of the present invention can be obtained by replacing the corresponding raw materials according to the contents described in the above-mentioned synthesis examples, or referring to the preparation methods described in the invention summary.

Table 88 Physical properties and structural characterization of compounds

Biological Activity Assay Example

The compound of the invention exhibits good activity against various pathogens in the agricultural field.

Example 4: Bactericidal activity assay

(1) In-house in vivo activity measurement

Method for testing the in vivo efficacy of bacterial fruit spot of melon, bacterial angular spot of cucumber and soft rot of Chinese cabbage: dissolve the test compound (compound of formula (I), intermediate V) with a small amount of dimethyl sulfoxide, dilute to the required concentration, and set up a blank control. Ensure that the front and back of the leaves are evenly coated with the drug during spraying. Adjust the cultured pathogenic bacteria solution to the required concentration and spray the plant leaves with the pathogen. Place the treated plants in an artificial climate chamber, and then transfer them to a greenhouse for normal cultivation. After the blank control becomes ill, investigate the control efficacy of the agent.

Test method for in vivo efficacy of citrus canker: streak the canker bacteria stored at ultra-low temperature on a solid culture medium, pick the activated single colony and culture it in a liquid culture medium for shaking, centrifuge and discard the supernatant, then add sterile water to resuspend the bacteria for inoculation. Dissolve the test compound with a small amount of dimethyl sulfoxide and prepare it to the required concentration of the test, and set up a blank control. Select two-year-old disease-free citrus cultivated in a greenhouse, and spray the test compound solution (compound of formula (I), intermediate V) evenly on the plants to cover the front and back of the leaves. After natural drying in the shade, use a spray method to evenly spray the citrus canker bacteria suspension on the plants to cover the front and back of the leaves, and investigate after 5-7 days.

The protective effect of some compounds on Chinese cabbage soft rot in vivo:

At a dosage of 600 mg/L, compounds 1-2, 1-8, 7-8, 27-8, 76-8, 77-9, 78-2, 79-8, 80-8, 81-9, 82-8, 86-2, M-75, M-77, M-83, M-84, and M-85 had an efficacy greater than 60%;

The in vivo protective effect of some compounds on cucumber angular leaf spot:

At a dosage of 600 mg/L, compounds 1-2, 1-3, 1-4, 1-8, 2-8, 7-8, 27-8, 36-8, 78-9, 81-2, 81-9, 82-8, 85-2, 86-2, M-1, M-2, M-36, M-82, and M-83 had an efficacy greater than 60%;

The in vivo protective effect of some compounds on melon fruit spot disease:

At a dosage of 600 mg/L, compounds 1-2, 1-8, 27-8, 36-8, 76-8, 80-8, and 81-8 had an efficacy greater than 60%;

In vivo activity of some compounds against citrus canker:

At a dosage of 300 mg/L, compounds 1-2, 1-8, 7-8, 76-8, 79-8, 80-8, 81-8, 86-8, 82-9, and 81-2 had a protective effect greater than 90%.

(2) In vitro activity assay

Cabbage black rot, Chinese cabbage soft rot, grape root cancer, rice streak disease, tobacco wildfire, citrus canker, kiwi canker, rice bacterial leaf blight, rice bacterial basal rot, walnut black spot, peach bacterial perforation, tomato bacterial wilt, melon bacterial fruit spot, cucumber bacterial angular spot, tomato canker In vitro control efficacy test method: using an in vitro high-throughput method, the test compound (compound of formula (I), intermediate V) is dissolved in a small amount of dimethyl sulfoxide to prepare a mother solution of the required concentration for the test, and a blank control is set at the same time. The pathogenic bacteria are shaken in LB liquid culture medium in advance, and the bacterial solution is adjusted to the required concentration and then mixed with the required amount of compound mother solution for the test in a microplate. The OD values of different treatments are measured by an ELISA instrument to calculate the control efficacy.

At a dosage of 100 mg/L, the in vitro inhibition rates of some compounds on cabbage black rot, Chinese cabbage soft rot, grape root cancer, rice streak disease, tobacco wildfire, citrus canker, kiwi canker, rice bacterial leaf blight, rice bacterial basal rot, walnut black spot, peach bacterial punch hole, tomato bacterial wilt, melon bacterial fruit spot, cucumber bacterial angular spot, and tomato canker reached 100%: 1-2, 1-8, 36-8, 1-8, 73-8, 76-8, 77-8, 78-8, 79-8, 80-8, 81-8, 83-8, 86-8, 74-9, 75-9, 82-9, 85-9, 73-2, 74-2, 75-2, 77-2, 80-2, 81-2, 83-2, and 86-2.

Example 5: Determination of fungicidal activity

In vivo protective activity assay

The determination method is as follows: adopt the living potted plant determination method, that is, the sample of the compound to be tested is dissolved with a small amount of solvent (the type of solvent is such as acetone, methanol, DMF, etc., and is selected according to its solubility for the sample, and the volume ratio of the solvent amount to the spray liquid amount is equal to or less than 0.05), and diluted with water containing 0.1% Tween 80 to prepare the required concentration of the test solution. On the crop sprayer, the test solution is sprayed on the disease host plant (the host plant is a standard potted seedling cultivated in a greenhouse), and the disease is inoculated 24 hours later. According to the characteristics of the disease, the diseased plants that need to be cultivated with temperature control and moisture retention are inoculated and placed in an artificial climate chamber for cultivation. After the disease infection is completed, they are moved to the greenhouse for cultivation. The diseased plants that do not need moisture retention cultivation are directly inoculated and cultivated in the greenhouse. After the control is fully diseased (usually one week), the disease prevention effect of the compound is evaluated.

The in vivo protective activity test results of some compounds are as follows:

In vivo protective activity against cucumber downy mildew:

At a dosage of 400 ppm, compounds such as 1-2, 1-3, 1-4, 2-8, 7-8, 27-8, 27-9, 77-2, 77-8, 78-8, 79-8, 80-8, 82-8, 83-8, 84-8, 85-8, 86-8, M-77, M-78, M-79, M-80, and M-83 have an efficacy of more than 80% against cucumber downy mildew.

In vivo protective activity against cucumber anthracnose:

At a dosage of 400 ppm, compounds such as 27-9, 29-2, 76-2, 77-8, 79-8, 80-8, 85-2, 85-8, 86-8, M-77, and M-83 have a protective effect of more than 80% against cucumber anthracnose.

In vivo protective activity against wheat scab:

At a dosage of 400 ppm, compounds such as 78-8, 80-8, 82-8, 83-8, etc. have a protective effect of more than 80% against wheat fusarium head blight.

In vivo protective activity against rice sheath blight:

At a dosage of 400 ppm, compounds such as 73-2, 74-2, 76-2, 77-2, 78-8, 79-2, 79-8, 80-8, 81-2, 81-8, 82-2, 83-2, 84-2, 84-8, M-83, and M-86 have a protective effect of more than 80% against rice sheath blight.

In vivo protective activity against corn rust:

At a dosage of 400 ppm, compounds such as 1-2, 1-3, 1-4, 2-8, 7-8, 27-8, 29-8, 77-8, 78-8, 79-8, 80-8, 81-8, 82-8, 83-8, 84-8, 85-8, 86-8, M-85, and M-86 have a protective effect of more than 80% against corn rust.

In vivo protective activity against cucumber powdery mildew:

At a dosage of 400 ppm, compounds such as 73-2, 77-8, 79-8, 80-8, 82-2, 84-8, 85-8, and M-1 have a protective effect of more than 80% against cucumber powdery mildew.

(3) Test results of some compounds and control drugs

Comparative test of the activity of some compounds and control agents on Chinese cabbage soft rot or cucumber angular leaf spot. The test results are shown in Table 89.

Table 89 In vivo protective activity (Chinese cabbage soft rot)

From the above data on the in vivo efficacy of Chinese cabbage soft rot, it can be seen that the above-obtained compounds show excellent effects in vivo. The effects of further reducing the dosage are shown in Table 90.

Table 90 In vivo protective activity (Chinese cabbage soft rot)

Table 91 In vivo protective activity (cucumber angular leaf spot)

From the above-mentioned in vivo protective efficacy data of cucumber angular leaf spot, it can be seen that the above-mentioned obtained compounds show excellent effects in vivo. The effects of further reducing the dosage are shown in Table 92.

Table 92 In vivo protective activity (cucumber angular leaf spot)

Claims (8)

1. A pyridazinone derivative, characterized in that: the compound represented by general formula I,
   

   Where:

   _R1 is selected from halogen;

   _R2 is selected from hydrogen, halogen, nitro, cyano, cyano _C1 - _C12 alkyl, _C3 - _C12 cycloalkyl, _C3 - _C12 epoxyalkyl, _C1 - _C12 alkyl, _C3 - _C12 cycloalkylmethylene, halogenated C1- _C12 alkyl _{, C1} - _C12 alkoxy _{C1 - C12} alkyl, hydroxy C1- _C12 alkyl, _C2 - _C12 alkenyl, C2 _{- C12} alkynyl, halogenated _C2 - _C12 alkenyl, halogenated _C2 - _C12 alkynyl, C1- _C12 alkoxycarbonyl, _C1 - _C12 alkoxycarbonyl _C1 - _C12 alkyl or dimethylamino C1- _C12 alkyl, aryl _{, aryl C1} - _C4 alkyl, heteroaryl, heteroaryl C1 _{- C12 4} alkyl;

   _R3 is selected from hydrogen, halogen, hydroxyl, mercapto, amino, cyano, nitro, _C1 - _C12 alkyl, halogenated C1- _C12 alkyl, _C1 - _C12 alkoxy, halogenated _C1 - _C12 alkoxy, _C1 - _C12 alkylthio, halogenated _C1 - _{C12 alkylthio} , _C3 - _C12 cycloalkyl, _C1 - _C12 alkylamino;

   n is 1, 2 or 3;

   M is selected from Li, Na, K, Zn, Cu, Mn, Fe, Co, Mg, Ca, Cr, Mo, Ni, Sn or Se.
2. The pyridazinone derivative according to claim 1, characterized in that: in the compound of general formula I,

   _R1 is selected from halogen;

   _R2 is selected from hydrogen, halogen, nitro, cyano, cyano _C1 - _C8 alkyl, _C3 - _C8 cycloalkyl, _C3 - _{C8 epoxyalkyl, C1-C8 alkyl , C3} - _C8 cycloalkylmethylene, halogenated C1- _C8 alkyl, _C1 - _C8 alkoxy _{C1 - C8} alkyl _, hydroxy C1- _C8 alkyl, _C2 - _C8 alkenyl, _C2 - _C8 alkynyl, halogenated _C2 - _C8 alkenyl, halogenated C2- _C8 alkynyl, _C1 - _C8 alkoxycarbonyl, _C1 - _C8 alkoxycarbonyl _C1 - _C8 alkyl or dimethylamino _C1 - _C8 alkyl, aryl, arylmethylene _, heteroaryl, heteroarylmethylene which are unsubstituted or substituted by 1 to 3 _R3 ;

   _R3 is selected from hydrogen, halogen, hydroxyl, mercapto, amino, cyano, nitro, C1-C8 alkyl, halogenated _C1 - _{C8 alkyl} , _C1 - _C8 alkoxy, halogenated _C1 - _C8 alkoxy, _C1 - _C8 alkylthio, halogenated _{C1 - C8} alkylthio, _C3 - _C8 cycloalkyl, _C1 - _C8 alkylamino;

   n is 1, 2 or 3;

   M is selected from Li, Na, K, Zn, Cu, Mn, Fe, Co, Mg, Ca, Cr, Mo, Ni, Sn or Se.
3. The pyridazinone derivative according to claim 2, characterized in that:

   _R1 is selected from halogen;

   _R2 is selected from hydrogen, halogen, nitro, cyano, cyano _C1 - _C4 alkyl, _C3 - _C4 cycloalkyl, _C3 - _C4 epoxyalkyl, _C1 - _C4 alkyl, _C3 - _C4 cycloalkylmethylene, halogenated C1- _C4 alkyl, _C1 - _C4 alkoxy _{C1 - C4} alkyl _, hydroxy C1- _C4 alkyl, _C2 - _C4 alkenyl, _C2 - _C4 alkynyl, halogenated _{C2 - C4} alkenyl, halogenated _C2 - _C4 alkynyl, _C1 - _C4 alkoxycarbonyl, _C1 - _C4 alkoxycarbonyl _C1 - _C4 alkyl or dimethylamino C1- _C4 alkyl, aryl, arylmethylene, heteroarylmethylene which are unsubstituted or substituted by 1-2 _R3 ;

   _R3 is selected from hydrogen, halogen, hydroxyl, mercapto, amino, cyano, nitro, C1- _{C4 alkyl, halogenated C1-C4 alkyl , C1-C4 alkoxy, halogenated C1-C4 alkoxy, C1-C4 alkylthio, halogenated C1-C4 alkylthio , C3 - C4 cycloalkyl , C1 - C4 alkylamino ;}

   n is 1, 2 or 3;

   M is selected from Li, Na, K, Zn, Cu, Mn, Fe, Co, Mg, Ca, Cr, Mo, Ni, Sn or Se.
4. The pyridazinone derivative according to claim 3, characterized in that:

   _R1 is selected from fluorine, chlorine, bromine or iodine;

   _R2 is selected from hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, cyano _C1 - _C4 alkyl, _C3 - _C4 cycloalkyl _, C3- _C4 epoxyalkyl, _C1 - _C4 alkyl, _C3 - _{C4 cycloalkylmethylene, halogenated C1-C4 alkyl , C1 - C4} alkoxy _C1 - _C4 alkyl, hydroxy C1- _C4 alkyl, _C2 - _C4 alkenyl, _C2 - _C4 alkynyl, _C1 - _C4 alkoxycarbonyl, _C1 - _C4 alkoxycarbonyl _C1 - _C4 alkyl or dimethylamino _C1 - _C4 alkyl, aryl substituted with one _R3 , arylmethylene, heteroarylmethylene;

   _R3 is selected from hydrogen, halogen, hydroxyl, mercapto, amino, cyano, nitro, C1-C4 alkyl, halogenated _{C1 - C4} alkyl, _C1 - _C4 alkoxy, halogenated _C1 - _C4 alkoxy, _C1 - _C4 alkylthio, halogenated _C1 - _{C4 alkylthio} ;

   n is 1, 2 or 3;

   M is selected from K, Na, Ca, Mg, Fe, Mn, Zn, Cu, Se.
5. The pyridazinone derivative according to claim 4, characterized in that:

   _R1 is selected from chlorine and bromine;

   _R is selected from hydrogen, chlorine, bromine, nitro, cyano, cyanoethyl, cyclopropyl, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, cyclopropylmethylene, monofluoromethyl, monochloromethyl, difluoromethyl, dichloromethyl, trifluoromethyl, trichloromethyl, trifluoroethyl, pentafluoroethyl, heptafluoroisopropyl, methoxymethylene, methoxyethyl, ethoxymethylene, hydroxyethyl, allyl, propargyl, methoxycarbonyl, methoxycarbonylmethylene or dimethylaminomethylene, phenyl, benzyl, 2-chloropyridin-5-methylene, 2-chloro-thiazole-5-methylene, furan-2-methylene;

   n is 1, 2 or 3;

   M is selected from K, Na, Ca, Mg, Fe, Mn, Zn, Cu, Se.
6. A method for preparing the compound of general formula I as claimed in claim 1, characterized in that: the reaction formula is as follows:
   

   When M is Li, Na or K, the compound of formula I can be prepared by reacting the intermediate V with a base containing Li, Na or K in a suitable solvent to obtain the corresponding compound of formula I.

   When M is Zn, Cu, Mn, Mg, Ca, Fe, Co, Cr, Mo, Ni, Sn or Se, the intermediate V can be reacted with an inorganic salt containing Zn, Cu, Mn, Mg, Ca, Fe, Co, Cr, Mo, Ni, Sn or Se in a suitable solvent under alkaline conditions to obtain the corresponding compound of formula I.
7. A use of the pyridazinone derivatives represented by the general formula I for preparing fungicides and bactericides in agriculture or other fields.
8. A use of the intermediate (V) compound according to claim 6 as a fungicide or bactericide in agriculture or forestry.